Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

doi:10.1183/09031936.00136312

Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

The Faculty of Medicine and Life Sciences

World Health Organization
University of Sassari
Albert Einstein College of Medicine
University of California at Davis
McGill University
Hospital de Infecciosas Francisco Javier Muñiz
Instituto Mexicano del Seguro Social
University of Insubria
VA Medical Center
Stellenbosch University
Harvard University
Centers for Disease Control and Prevention

Research output: Contribution to journal › Article › peer-review

231 Citations (Scopus)

Abstract

The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

Original language	English
Pages (from-to)	169-179
Number of pages	11
Journal	European Respiratory Journal
Volume	42
Issue number	1
DOIs	https://doi.org/10.1183/09031936.00136312
Publication status	Published - 1 Jul 2013

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10.1183/09031936.00136312

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@article{62d07202d0a2433b948416ce3b1b3036,

title = "Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis",

abstract = "The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95\%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.",

author = "\{Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB\} and Migliori, \{Giovanni Battista\} and Giovanni Sotgiu and Gandhi, \{Neel R.\} and Dennis Falzon and Kathryn DeRiemer and Rosella Centis and Hollm-Delgado, \{Maria Graciela\} and Domingo Palmero and Carlos P{\'e}rez-Guzm{\'a}n and Vargas, \{Mario H.\} and Lia D'Ambrosio and Antonio Spanevello and Melissa Bauer and Chan, \{Edward D.\} and Schaaf, \{H. Simon\} and Salmaan Keshavjee and Holtz, \{Timothy H.\} and Dick Menzies and S. Ahuja and D. Ashkin and M. Avendano and R. Banerjee and Bayona, \{J. N.\} and Becerra, \{M. C.\} and A. Benedetti and M. Burgos and Chiang, \{C. Y.\} and H. Cox and Dung, \{N. H.\} and D. Enarson and K. Flanagan and J. Flood and L. Garcia-Garcia and Granich, \{R. M.\} and Iseman, \{M. D.\} and Jarlsberg, \{L. G.\} and Kim, \{H. R.\} and Koh, \{W. J.\} and J. Lancaster and C. Lange and \{De Lange\}, \{W. C.M.\} and V. Leimane and Leung, \{C. C.\} and J. Li and Mishustin, \{S. P.\} and Mitnick, \{C. D.\} and M. Narita and P. O'Riordan and M. Pai and V. Riekstina",

year = "2013",

month = jul,

day = "1",

doi = "10.1183/09031936.00136312",

language = "English",

volume = "42",

pages = "169--179",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "1",

}

TY - JOUR

T1 - Drug resistance beyond extensively drugresistant tuberculosis

T2 - Individual patient data meta-analysis

AU - Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

AU - Migliori, Giovanni Battista

AU - Sotgiu, Giovanni

AU - Gandhi, Neel R.

AU - Falzon, Dennis

AU - DeRiemer, Kathryn

AU - Centis, Rosella

AU - Hollm-Delgado, Maria Graciela

AU - Palmero, Domingo

AU - Pérez-Guzmán, Carlos

AU - Vargas, Mario H.

AU - D'Ambrosio, Lia

AU - Spanevello, Antonio

AU - Bauer, Melissa

AU - Chan, Edward D.

AU - Schaaf, H. Simon

AU - Keshavjee, Salmaan

AU - Holtz, Timothy H.

AU - Menzies, Dick

AU - Ahuja, S.

AU - Ashkin, D.

AU - Avendano, M.

AU - Banerjee, R.

AU - Bayona, J. N.

AU - Becerra, M. C.

AU - Benedetti, A.

AU - Burgos, M.

AU - Chiang, C. Y.

AU - Cox, H.

AU - Dung, N. H.

AU - Enarson, D.

AU - Flanagan, K.

AU - Flood, J.

AU - Garcia-Garcia, L.

AU - Granich, R. M.

AU - Iseman, M. D.

AU - Jarlsberg, L. G.

AU - Kim, H. R.

AU - Koh, W. J.

AU - Lancaster, J.

AU - Lange, C.

AU - De Lange, W. C.M.

AU - Leimane, V.

AU - Leung, C. C.

AU - Li, J.

AU - Mishustin, S. P.

AU - Mitnick, C. D.

AU - Narita, M.

AU - O'Riordan, P.

AU - Pai, M.

AU - Riekstina, V.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

AB - The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

UR - https://www.scopus.com/pages/publications/84880158505

U2 - 10.1183/09031936.00136312

DO - 10.1183/09031936.00136312

M3 - Article

C2 - 23060633

AN - SCOPUS:84880158505

SN - 0903-1936

VL - 42

SP - 169

EP - 179

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 1

ER -

Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

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